Research showing biomarker link between ME and Long COVID

Nature: Post-Covid ME/CFS and Biomarkers Association with Symptom Severity

Nature has an article on German research showing the overlap between ME/CFS and Long COVID and possible biomarkers.


A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19.

Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily lives.

19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients.

Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.


Long-term health consequences following mild COVID-19 are poorly understood yet but have been feared based on observations from SARS-CoV-1. Here many patients were reported who developed a severe postinfectious syndrome with persistent fatigue, muscle pain, shortness of breath, and mental symptoms independent of illness severity.

Various pathogens including Epstein-Barr virus (EBV), enteroviruses, and dengue viruses are known to trigger myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in a subset of patients. It is unclear yet if pathomechanisms of postinfectious fatigue syndromes may vary depending on the pathogen.

ME/CFS is a debilitating chronic disease with a worldwide prevalence of 0.3–0.8%. Profound mental and physical fatigue, PEM, cognitive impairment, chronic pain, and orthostatic intolerance are key symptoms of ME/CFS. The best discriminating symptoms distinguishing ME/CFS from chronic fatigue in multiple sclerosis were flu-like symptoms and the intolerance to mental and physical exertion triggering PEM for more than 14 h14.

ME/CFS is classified by the WHO as a neurological disease with G93.3 in the International Classification of Diseases 10th revision (ICD-10). Although the pathomechanisms are not well understood yet, there is ample evidence of immune, autonomous nervous system and metabolic dysregulation. There is emerging evidence that postinfectious ME/CFS has an autoimmune mechanism…

We hypothesized that COVID-19 can lead to a persistent fatigue syndrome which fulfills diagnostic criteria of ME/CFS and that patients suffering from ME/CFS display specific characteristics. Our findings confirm initial concerns that COVID-19 leads to persistent fatigue syndromes in a subset of young individuals following mild to moderate infectious disease.


Taken together, our study provides evidence that patients following mild COVID-19 develop a chronic syndrome fulfilling diagnostic criteria of ME/CFS in a subset.

By defining and characterizing subgroups of PCS [Post-COVID Syndrome] patients we could identify associations of HGS [Hand Grip Strength] with biomarkers which may indicate hypoperfusion and inflammation as potential pathomechanisms.

We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients. At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis.

Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.

Shopping Basket